-->PONE-D-25-51694-->-->Cost-effectiveness analysis of mammography screening for early detection of breast cancer in Nigeria-->-->PLOS One

Dear Dr. Nduka,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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We look forward to receiving your revised manuscript.

Kind regards,

Daniele Ugo Tari, M.D.

Academic Editor

PLOS One

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https://bmjpublichealth.bmj.com/content/2/2/e001356.

https://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0006124

In your revision ensure you cite all your sources (including your own works), and quote or rephrase any duplicated text outside the methods section. Further consideration is dependent on these concerns being addressed.

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Additional Editor Comments (if provided):

Dear Authors,

The manuscript addresses a policy-relevant question for Nigeria by modeling the cost-effectiveness of annual versus biennial mammography from age 40 using a lifetime Markov framework with DALYs and discounting, and it appropriately reports uncertainty analyses while drawing on local data where available. However, the authors need to address several issues before the findings can be interpreted confidently for policy. To be suitable for publication, the paper needs extensive revision.

I suggest to address all the reviewers' comments and to resubmit it.

Sincerely,

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

-->Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. -->

Reviewer #1: Partly

Reviewer #2: No

Reviewer #3: Partly

Reviewer #4: Yes

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-->2. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #1: Yes

Reviewer #2: I Don't Know

Reviewer #3: Yes

Reviewer #4: Yes

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-->3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.-->

Reviewer #1: No

Reviewer #2: Yes

Reviewer #3: No

Reviewer #4: Yes

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-->4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.-->

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

Reviewer #4: Yes

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-->5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)-->

Reviewer #1: Thank you for taking on a very relevant topic and using a modeling approach to explore the cost-effectiveness of breast cancer screening in Nigeria.

The Markov model you’ve used is appropriate, but several of the input values—like transition probabilities and utility scores—are taken from studies outside Nigeria or are outdated. It would help to either source more locally relevant data or explain clearly why these were used.

Assuming 100 percent screening participation is unrealistic in the Nigerian context. Please try modeling lower compliance rates or at least discuss how this assumption affects the results.

The sensitivity analysis section feels a bit thin. You could improve this by explaining the range used for each variable and maybe adding a tornado diagram to show which factors influence the outcome most.

There's no mention of ethical approval or waiver. Even though it’s a modeling study, this should be clarified in the manuscript.

The underlying data and model files haven’t been made publicly available. Please consider sharing them in a repository so others can replicate or build on your work.

The discussion would benefit from addressing real-world implementation challenges -things like infrastructure, funding, or public awareness that affect whether screening programs can actually be rolled out.

With these improvements, your paper could be much stronger and more useful for decision-makers and researchers alike.

Reviewer #2: If the primary objective of the manuscript is a cost-effectiveness analysis, it remains unclear why the authors extend their conclusions to the definition of screening guidelines, particularly with respect to starting age and screening interval.

The statement “Currently, there is no national breast cancer mammography screening program in Nigeria; hence, no national screening guidelines” (lines 58–59) is conceptually problematic. Guidelines do not necessarily follow the existence of a screening program. They may either be developed based on robust evidence tailored to a specific national context or be adapted from existing international guidance. In this manuscript, the authors themselves cite international recommendations (e.g. IARC) that, at a global level, recognize biennial mammography starting at age 50 for women at average risk (references 62–63). The rationale for departing from these established recommendations is not sufficiently justified.

The authors state that evaluating the cost-effectiveness of a national mammography screening program is crucial to ensure accessibility and that a modelling approach is appropriate given the lack of feasibility of trial-based evaluations in Nigeria. While this argument supports the use of modelling, it does not adequately explain how the authors arrive at a recommendation of annual mammography starting at age 40, which is not aligned with IARC recommendations. A cost-effectiveness model alone cannot replace the evidentiary basis required to define screening age and interval.

In addition, the model relies on DALYs as the primary outcome. It is generally accepted that cancer screening programs should primarily be evaluated on mortality reduction, as earlier diagnosis without a demonstrated effect on mortality is often considered a key argument against screening adoption. The use of DALYs may therefore limit the ability of the model to inform screening policy decisions, particularly with regard to overdiagnosis and overtreatment.

A further concern relates to the assumption (line 129) that all breast cancer patients undergo prompt and adequate treatment. This assumption appears inconsistent with the authors’ own introductory statement (line 55) highlighting that early diagnosis of breast cancer in Nigeria faces multiple challenges, resulting in late presentation. The implementation of a screening program presupposes the availability of timely and effective diagnostic and treatment pathways, which are not clearly demonstrated in the manuscript.

It is therefore difficult to understand how the cost-effectiveness model can robustly support conclusions such as those presented in lines 334 and 341, where mammography screening is described as cost-effective from the healthcare payer’s perspective and annual screening is identified as the optimal interval. These conclusions appear to go beyond what can reasonably be inferred from the modelling framework.

The authors also state that “the potential to reduce breast cancer mortality depends on increasing mammography screening rates and facilitating early-stage detection” (line 366). This assertion remains debated in the literature (see, for example, Autier et al., Evaluation of screening mammography effectiveness: The IARC recommendations of 2015 need revision, European Journal of Cancer, 2025). In this context, it is difficult to justify recommendations favoring mammography screening for Nigerian women aged 40–69 based on a DALY-based cost-effectiveness analysis that is not consistent with IARC guidance.

Finally, the statement regarding “current evidence on the increasing incidence of breast cancer in women aged 40–49” (lines 389–391) requires clearer justification and stronger referencing. At present, much of the observed increase in incidence in this age group is attributable to the introduction of screening itself, particularly in settings where screening was previously absent or has been recently extended to younger women. This phenomenon does not provide evidence of screening effectiveness and is widely regarded as a manifestation of overdiagnosis, with consequent overtreatment.

My comments focus on the coherence between the model assumptions, the interpretation of the results, and their implications for screening policy and clinical practice but as public health expert I may not be fully qualified to assess all the methodological nuances of the modelling approach itself. In my opinion in any case, the manuscript presents substantial conceptual and methodological limitations that in its current form prevent it from adequately supporting its main conclusions .

Reviewer #3: The manuscript evaluates the cost-effectiveness of annual versus biennial mammography for Nigerian women starting at age 40 using a lifetime Markov model with DALYs and 5% discounting. The question is policy-relevant and aligned with Nigeria’s cancer-control priorities, and the overall analytic approach is reasonable for screening evaluation. The authors also make a good-faith attempt to characterize uncertainty through sensitivity analyses and acceptability outputs, and they draw on Nigerian inputs where available, which improves local relevance.

However, several issues need to be corrected or more rigorously handled before the findings can be interpreted confidently for policy. First, the stated mortality structure—namely that only stage IV patients can die from breast cancer—is not clinically plausible and is likely to distort life-years/DALYs and therefore the ICER; moreover, the manuscript appears internally inconsistent on this point given the inclusion of stage-specific fatality parameters, so the authors should clarify what was actually implemented. In either case, the model should be revised to a realistic stage-specific mortality framework (or calibrated to observed survival), and the impact of alternative mortality structures should be explored in scenario analyses. Second, the model presumes that all breast cancer patients receive prompt and adequate treatment, which does not reflect real-world variability in access, timeliness, and completion of care in Nigeria and may overstate screening benefits. The analysis should incorporate scenarios with constrained access, treatment delays, and incomplete treatment (including stage-specific treatment coverage if possible), and clearly report how these change outcomes and conclusions. Third, the model description should explicitly specify how screening uptake, adherence across rounds, diagnostic follow-up completion after abnormal screens, and loss-to-follow-up are represented in the base case. If any of these are not modeled or are implicitly assumed to be perfect (e.g., 100% uptake/adherence/follow-up), that should be stated plainly and tested with plausible ranges because these parameters strongly influence both effectiveness and cost-effectiveness—particularly in settings where participation and follow-up can be substantial bottlenecks. Fourth, the exclusion of implementation and other non-medical program costs (e.g., outreach, invitation/recall systems, administration, quality assurance, patient navigation, and program management) will tend to bias results in favor of screening. Even if Nigeria-specific estimates are limited, the authors should include plausible ranges informed by comparable programs and conduct scenario analyses to assess whether conclusions remain robust once these costs are incorporated. Finally, the current data/model availability statement is unlikely to enable full replication of a lifetime decision model. Sharing the model file/code and providing a complete parameter table (including all transition probabilities, screening and follow-up pathways, treatment assumptions, the full costing build-up, and sources) as supplementary material would substantially strengthen transparency, reproducibility, and confidence in the results.

Reviewer #4: It would be appropriate to highlight more clearly the originality of the study by emphasizing how it differs from and adds to existing studies.

In addition, it would be appropriate to describe more clearly—also through a dedicated paragraph—the characteristics of the Nigerian healthcare system and of mammography screening.

Finally, it would also be appropriate to highlight potential future directions for the research.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

Reviewer #4: No

**********

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-->PONE-D-25-51694R1-->-->Cost-effectiveness analysis of mammography screening for early detection of breast cancer in Nigeria-->-->PLOS One

Dear Dr. Nduka,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by May 09 2026 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:-->

• A letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

-->

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

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We look forward to receiving your revised manuscript.

Kind regards,

Daniele Ugo Tari, M.D.

Academic Editor

PLOS One

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Additional Editor Comments:

Dear Authors,

The paper has been widely revised according to the reviewers' suggestions.

Nevertheless, there are a few observations from reviewer n. 2 requiring revision.

Sincerely,

[Note: HTML markup is below. Please do not edit.]

Reviewer's Responses to Questions

-->Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.-->

Reviewer #2: All comments have been addressed

Reviewer #4: All comments have been addressed

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-->2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. -->

Reviewer #2: (No Response)

Reviewer #4: Yes

**********

-->3. Has the statistical analysis been performed appropriately and rigorously? -->

Reviewer #2: I Don't Know

Reviewer #4: Yes

**********

-->4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.-->

Reviewer #2: Yes

Reviewer #4: Yes

**********

-->5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.-->

Reviewer #2: Yes

Reviewer #4: Yes

**********

-->6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)-->

Reviewer #2: Overall, the revisions introduced by the authors respond satisfactorily to the previous comments and represent a meaningful improvement of the manuscript. It is understandable that the modelling approach focuses on the 40–49 age group, which currently does not comply with international recommendations that generally indicate the start of screening at age 50. This limitation is correctly acknowledged in the manuscript but the issue might be further contextualized not only by recalling references 60–63, which, in my opinion, do not have the authority to be considered a valid alternative to IARC recommendations, but also by considering perhaps the demographic characteristics of Nigeria, whose relatively young median age may partly support the authors’ focus on the 40–49 age group. Nevertheless, the question of the transferability of a purely economic modelling analysis to a real-world implementation context remains open, particularly when the target age group and screening frequency differ from those universally recommended by IARC. In this respect, the practical implementation considerations discussed on page 22 add value to the manuscript. On the one hand, they outline possible pathways for translating the theoretical modelling results into real-world practice; on the other hand, they appropriately acknowledge the limitations inherent to a theoretical economic model when informing screening policy decisions.

Reviewer #4: (No Response)

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Reviewer #2: Yes:  Francesco Gongolo

Reviewer #4: No

**********

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-->

Cost-effectiveness analysis of mammography screening for early detection of breast cancer in Nigeria

PONE-D-25-51694R2

Dear Dr. Nduka,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Daniele Ugo Tari, M.D.

Academic Editor

PLOS One

Additional Editor Comments (optional):

Dear Authors,

All comments have been addressed.

The paper has significantly improved and consequently, it can be accepted for publication.

Sincerely,

Reviewers' comments: